Mild and selective activation and substitution of strong aliphatic C-F bonds.

A procedure for chemoselectively manipulating the strong aliphatic CF bond with direct transformation into a CN bond under mild conditions is reported. The activation and subsequent substitution of primary alkyl fluorides is mediated by La[N(SiMe3)(2)](3), and results in high to excellent yields of tertiary amines. The methodology displays high selectivity towards the C(sp(3))F bond, and a variety of secondary amines are applicable as nucleophiles. Mechanistic investigations reveal a reaction that is first order with respect to [La[N(SiMe3)(2)](3)], [(RRNH)-R-1-N-2], and [alkyl fluoride], and a 6-membered cyclic transition state is proposed. In addition, (HNMR)-H-1 spectroscopy shows that La[N(SiMe3)(2)](3) is the active species involved in the substitution and that protonolysis of the amine, yielding La[(NRR2)-R-1](3), lowers the reactivity.